December 21, 2023

VIEW TRANSCRIPT

RSV

The Annual Economic Burden of Respiratory Syncytial Virus in Adults in the United States
A cost-of-illness model was developed to estimate the annual societal burden of RSV in US adults aged ≥60 years. Additional analyses were conducted to estimate the burden of hospitalized RSV in all adults aged 50-59 years and in adults aged 18-49 years with potential RSV risk factors. US adults aged ≥60 years, the model estimated 4.0 million annual RSV cases (95% UI, 2.7-5.6 million) and an annual economic burden of $6.6 billion (95% UI, $3.1-$12.9 billion; direct medical costs, $2.9 billion; indirect costs, $3.7 billion). The 4% of RSV cases that were hospitalized contributed to 94% of direct medical costs. Additional analyses estimated $422 million in annual hospitalization costs among all adults aged 50-59 years. Among adults aged 18-49 years with RSV risk factors, annual per capita burden was highest among people with congestive heart failure at $51,100 per 1000 people. Note: This is just adults. Add in the children and the number only gets bigger.

Flu

Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age
These are results from a cluster-randomized observational study. Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018–2019 and 2019–2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. The study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1,386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2,435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1,000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1,000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P=0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P=0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines.
Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations and Emergency Department Visits in Infants
These are the results of a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to 2020 influenza seasons. Infants younger than 6 months with an ED visit or hospitalization for acute respiratory illness were included from 7 pediatric medical institutions in US cities. Control infants with an influenza-negative molecular test were included for comparison. Data were analyzed from June 2022 to September 2023. Of 3,764 infants (223 with influenza and 3,541 control infants), 2,007 (53%) were born to mothers who were vaccinated during pregnancy. Overall vaccine effectiveness in infants was 34% (95% CI, 12 to 50), 39% (95% CI, 12 to 58) against influenza-associated hospitalizations, and 19% (95% CI, −24 to 48) against ED visits. Among infants younger than 3 months, effectiveness was 53% (95% CI, 30 to 68). Effectiveness was 52% (95% CI, 30 to 68) among infants with mothers who were vaccinated during the third trimester and 17% (95% CI, −15 to 40) among those with mothers who were vaccinated during the first or second trimesters.

COVID: Children and other Vulnerable Populations

Risk of Severe Maternal Morbidity Associated with SARS-CoV-2 Infection During Pregnancy
Here are the results from a national cohort study of 93,624 deliveries occurring between 11 March 2020 and 1 July 2021 using medical claims information from the OptumLabs® Data Warehouse. SARS-CoV-2 infection was identified from diagnostic and laboratory testing claims records. 4.8% of deliveries had a record of SARS-CoV-2 infection: 27.0% <7 days before delivery, 13.5% within 7-30 days of delivery, and 59.5% earlier in pregnancy. Compared to uninfected pregnancies, the adjusted risk of Severe maternal morbidity (SMM) was 2.22 times higher (95%CI 1.97, 2.48) among those infected <7 days before delivery and 1.66 times higher (95%CI 1.23, 2.08) among those infected 7-30 days before delivery. The highest risks were observed for adult respiratory distress syndrome (aRR 13.24; 95%CI 12.86, 13.61) and acute renal failure (aRR 3.91; 95%CI 3.32, 4.50).

COVID: Early Viral Phase

Optimal Timing of Nirmatrelvir/ritonavir Treatment after COVID-19 Symptom Onset or Diagnosis: Target Trial Emulation
Investigators performed two territory-wide, retrospective cohort analyses using the target trial emulation approach to examine the effect of the timing of nirmatrelvir/ritonavir initiation on the incidence of all-cause mortality, all-cause hospitalization, and viral burden rebound (VBR) among all adult (age ≥18 years) patients who had initiated nirmatrelvir/ritonavir in the Hong Kong Special Administrative Region (SAR), China, between 16 March 2022 (the date when nirmatrelvir/ritonavir were first available for use in Hong Kong) and 15 January 2023. During our study period, COVID-19 infections in Hong Kong were predominately caused by Omicron and its subvariants. The authors point out that a number of case reports and studies have reported symptom recurrence or viral burden rebound (VBR) after initial recovery upon completing a standard 5-day course of nirmatrelvir/ritonavir. It has been hypothesized that initiating nirmatrelvir/ritonavir too early after symptom onset or diagnosis may, in some cases, be associated with VBR and symptom recurrence. Due to early suppression of viral replication by nirmatrelvir/ritonavir, the host adaptive immune response may not have had sufficient stimulus and time to fully develop by the end of antiviral therapy, thus allowing any remnant virus to subsequently resume replication and shedding. However, this hypothesis has not hitherto been tested against real-world clinical data. Early initiation was defined as a prescription of nirmatrelvir/ritonavir within 1 day from the date of COVID-19 diagnosis or first symptom onset (day 0–1). Late initiation was defined as prescription on or beyond days 2. Index date was defined as that of SARS-CoV-2 infection diagnosis or symptom onset, whichever occurred earlier. A total of 87,070 nirmatrelvir/ritonavir users who had confirmed diagnoses of SARS-CoV-2 infection between 16th March 2022 and 15th January 2023 were included in this analysis. Early initiation of nirmatrelvir/ritonavir (i.e., within 1 day of symptom onset or diagnosis) was associated with a significantly lower risk of 28-day all-cause mortality or hospitalization (ARR: 1.50%, 95% CI (1.17%, 1.80%), RR: 0.77, 95% CI (0.73, 0.82)) versus late initiation (2 or more days after symptom onset or diagnosis). A significantly lower risk was also observed if nirmatrelvir/ritonavir was initiated within 2 days of symptom onset or diagnosis versus 3 or more days (ARR: 2.25% (1.40%, 3.02%), RR: 0.70 (0.63, 0.79)), and within 3 days versus 4 or more days (ARR: 2.82% (0.65%, 5.40%), RR: 0.66 (0.50, 0.90)). Their data did suggest that early initiation of nirmatrelvir/ritonavir (0–1 days after symptom onset or diagnosis) may be associated with an elevated risk of VBR compared to late initiation (on or beyond 2 days) (ARR: −1.08% (−1.55%, −0.46%)) but they comment that a paucity of VBR events and wide confidence intervals introduces a high degree of uncertainty regarding VBR and that in vaccinated or boosted individuals there was no statistically significant correlation with VBR and timing of treatment.

COVID: The Late Phase/PASC/Long COVID

Long-term Outcomes Following Hospital Admission for COVID-19 versus Seasonal Influenza: A Cohort Study
In this cohort study the authors used the health-care databases of the US Department of Veterans Affairs. They analyzed data from 81,280 participants admitted to hospital for COVID-19 between March 1, 2020, and June 30, 2022, and 10,985 participants admitted to hospital for seasonal influenza between Oct 1, 2015, and Feb 28, 2019. Participants were followed up for up to 18 months to comparatively evaluate risks and burdens of death, a prespecified set of 94 individual health outcomes, ten organ systems, overall burden across all organ systems, readmission, and admission to intensive care. Over 18 months of follow-up, compared to seasonal influenza, the COVID-19 group had an increased risk of death (hazard ratio [HR] 1·51 [95% CI 1·45–1·58]), corresponding to an excess death rate of 8·62 (95% CI 7·55–9·44) per 100 persons in the COVID-19 group versus the influenza group. Compared to seasonal influenza, COVID-19 also had an increased risk of hospital readmission (excess rate 20·50 [95% CI 16·10–24·86] per 100 persons) and admission to intensive care (excess rate 9·23 [6·68–11·82] per 100 persons).
Risk of Arrhythmias following COVID-19: Nationwide Self-controlled Case Series and Matched Cohort Study
This study was based on national register data on all individuals in Sweden who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021. The outcome was incident cardiac arrhythmias: atrial arrhythmias; paroxysmal supraventricular tachycardias; bradyarrhythmias; and ventricular arrhythmias. These results are from a self-controlled case series study and a matched cohort study performed to determine the risk ratio for an arrhythmia event following COVID-19.A total of 1,057,174 exposed (COVID-19) individuals were included in the study as well as 4,074,844 matched unexposed individuals. The incidence rate ratio of atrial tachycardias, paroxysmal supraventricular tachycardias, and bradyarrhythmias was significantly increased up to 60, 180, and 14 days after COVID-19, respectively. In the matched cohort study, the risk ratio during Days 1–30 following COVID-19/index date was 12.28 (10.79–13.96), 5.26 (3.74–7.42), and 3.36 (2.42–4.68), respectively, for the three outcomes. The risks were generally higher in older individuals, in unvaccinated individuals, and in individuals with more severe COVID-19.